Hyperkinetic Movement Disorder Caused by the Recurrent c.892C>T NACC1 Variant
Komulainen-Ebrahim, Jonna; Kangas, Salla M; López-Martín, Estrella; Feyma, Timothy; Scaglia, Fernando; Martínez-Delgado, Beatriz; Kuismin, Outi; Suo-Palosaari, Maria; Carr, Lucinda; Hinttala, Reetta; Kurian, Manju A; Uusimaa, Johanna (2024-05-02)
John Wiley & Sons
02.05.2024
Komulainen-Ebrahim, J., Kangas, S.M., López-Martín, E., Feyma, T., Scaglia, F., Martínez-Delgado, B., Kuismin, O., Suo-Palosaari, M., Carr, L., Hinttala, R., Kurian, M.A. and Uusimaa, J. (2024), Hyperkinetic Movement Disorder Caused by the Recurrent c.892C>T NACC1 Variant. Mov Disord Clin Pract, 11: 708-715. https://doi.org/10.1002/mdc3.14051
https://creativecommons.org/licenses/by/4.0/
© 2024 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
https://creativecommons.org/licenses/by/4.0/
© 2024 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
https://creativecommons.org/licenses/by/4.0/
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202405223842
https://urn.fi/URN:NBN:fi:oulu-202405223842
Tiivistelmä
Abstract
Background:
Genetic syndromes of hyperkinetic movement disorders associated with epileptic encephalopathy and intellectual disability are becoming increasingly recognized. Recently, a de novo heterozygous NACC1 (nucleus accumbens-associated 1) missense variant was described in a patient cohort including one patient with a combined mitochondrial oxidative phosphorylation (OXPHOS) deficiency.
Objectives
The objective is to characterize the movement disorder in affected patients with the recurrent c.892C>T NACC1 variant and study the NACC1 protein and mitochondrial function at the cellular level.
Methods:
The movement disorder was analyzed on four patients with the NACC1 c.892C>T (p.Arg298Trp) variant. Studies on NACC1 protein and mitochondrial function were performed on patient-derived fibroblasts.
Results:
All patients had a generalized hyperkinetic movement disorder with chorea and dystonia, which occurred cyclically and during sleep. Complex I was found altered, whereas the other OXPHOS enzymes and the mitochondria network seemed intact in one patient.
Conclusions:
The movement disorder is a prominent feature of NACC1-related disease.
Background:
Genetic syndromes of hyperkinetic movement disorders associated with epileptic encephalopathy and intellectual disability are becoming increasingly recognized. Recently, a de novo heterozygous NACC1 (nucleus accumbens-associated 1) missense variant was described in a patient cohort including one patient with a combined mitochondrial oxidative phosphorylation (OXPHOS) deficiency.
Objectives
The objective is to characterize the movement disorder in affected patients with the recurrent c.892C>T NACC1 variant and study the NACC1 protein and mitochondrial function at the cellular level.
Methods:
The movement disorder was analyzed on four patients with the NACC1 c.892C>T (p.Arg298Trp) variant. Studies on NACC1 protein and mitochondrial function were performed on patient-derived fibroblasts.
Results:
All patients had a generalized hyperkinetic movement disorder with chorea and dystonia, which occurred cyclically and during sleep. Complex I was found altered, whereas the other OXPHOS enzymes and the mitochondria network seemed intact in one patient.
Conclusions:
The movement disorder is a prominent feature of NACC1-related disease.
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